Pathways in the brain, heart, and lung influenced by SARS-CoV-2 NSP6 and SARS-CoV-2 regulated miRNAs: an in silico study hinting cancer incidence

The influence of SARS-CoV-2 non-structural protein in the host's tissue-specific complexities remains a mystery and needs more in-depth attention because of COVID-19 recurrence and long COVID. Here we investigated the influence of SARS-CoV-2 transmembrane protein NSP6 (Non-structural protein 6) in three major organs - the brain, heart, and lung in silico. To elucidate the interplay between NSP6 and host proteins, we analyzed the protein-protein interaction network of proteins interacting with NSP6 interacting proteins. Reported host interacting partners of NSP6 were ATP5MG, ATP6AP1, ATP13A3, and SIGMAR1. Pathway enrichment analyses provided global insights into biological pathways governed by differentially regulated genes in the three tissues after COVID-19 infection. Hub genes of tissue-specific protein interactome were analysed for drug targets and many were found. miRNA-gene network for the tissue-specific regulated proteins was sought. Comparing this list with the gene list targetted by SARS-CoV-2 regulated miRNAs, we found three and two common genes in the brain and lung respectively. Among the five common proteins revealed as potential therapeutic targets across the three tissues, four non-approved drugs and one approved drug could target Galectin 3 (LGALS3) and AIFM1 respectively. Increased expression of LGALS3 (that was upregulated in the heart after COVID-19 infection) is observed in multiple cancers and acts as a modulator for tumor progression. COVID-19 infection also causes myocardial inflammation and heart failure (HF). HF is observed to be increasing cancer incidence. The present scenario of long COVID-19 and recurrent COVID-19 infections warrants in-depth studies to probe the effect of COVID-19 infection on increased cancer incidence. ### Competing Interest Statement The authors have declared no competing interest.